Barnes Kathleen C, Grant Audrey V, Hansel Nadia N, Gao Peisong, Dunston Georgia M
Division of Allergy and Clinical Immunology, Department of Medicine, The Johns Hopkins University, Baltimore, Maryland, USA.
Proc Am Thorac Soc. 2007 Jan;4(1):58-68. doi: 10.1513/pats.200607-146JG.
It has been well established that genetic factors strongly affect susceptibility to asthma and its associated traits. It is less clear to what extent genetic variation contributes to the ethnic disparities observed for asthma morbidity and mortality. Individuals of African descent with asthma have more severe asthma, higher IgE levels, a higher degree of steroid dependency, and more severe clinical symptoms than individuals of European descent with asthma but relatively few studies have focused on this particularly vulnerable ethnic group. Similar underrepresentation exists for other minorities, including Hispanics. In this review, a summary of linkage and association studies in populations of African descent is presented, and the role of linkage disequilibrium in the dissection of a complex trait such as asthma is discussed. Consideration for the impact of population stratification in recently admixed populations (i.e., European, African) is essential in genetic association studies focusing on African ancestry groups. With the most recent update on the International HapMap Project, efficient selection of haplotype tagging single nucleotide polymorphisms (htSNPs) for African Americans has accelerated and efficiency of htSNPs chosen from one population to represent other continental groups (e.g., African) has been demonstrated. Cutting-edge approaches, such as genomewide association studies, admixture mapping, and phylogenetic analyses, offer new opportunities for dissecting the genetic basis for asthma in populations of African descent.
遗传因素强烈影响哮喘易感性及其相关特征,这一点已得到充分证实。但遗传变异在多大程度上导致了哮喘发病率和死亡率方面存在的种族差异,目前尚不清楚。与患有哮喘的欧洲裔个体相比,患有哮喘的非洲裔个体哮喘更为严重,免疫球蛋白E(IgE)水平更高,对类固醇的依赖程度更高,临床症状也更严重,但针对这一特别脆弱的种族群体的研究相对较少。包括西班牙裔在内的其他少数族裔在研究中也同样代表性不足。在这篇综述中,我们总结了非洲裔人群中的连锁和关联研究,并讨论了连锁不平衡在剖析哮喘等复杂性状中的作用。在针对非洲裔群体的基因关联研究中,考虑近期混合人群(即欧洲裔、非洲裔)中群体分层的影响至关重要。随着国际人类基因组单体型图计划(International HapMap Project)的最新进展,为非裔美国人高效选择单倍型标签单核苷酸多态性(htSNP)的工作加速推进,并且已证明从一个群体中选择的htSNP代表其他大陆群体(如非洲群体)的效率。全基因组关联研究、混合映射和系统发育分析等前沿方法为剖析非洲裔人群哮喘的遗传基础提供了新机遇。